A HIDDEN FUNGAL TRIGGER: A CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Document Type

Conference Proceeding

Publication Date

7-17-2025

Publication Title

J Gen Intern Med

Keywords

amphotericin B, antibiotic agent, bilirubin, C reactive protein, etoposide, fibrinogen, hemoglobin, infliximab, steroid, acute kidney failure, adverse drug reaction, anemia, anterior cervical plate, antifungal therapy, autoimmunity, blood clotting disorder, blood culture, bone marrow biopsy, case report, cholestasis, clinical article, common bile duct stone, conference abstract, Crohn disease, cytopenia, diagnosis, drug therapy, drug withdrawal, endoscopic retrograde cholangiopancreatography, erythrophagocytosis, fatigue, fever, hemophagocytic syndrome, hepatosplenomegaly, histoplasmosis, human, human tissue, hyperbilirubinemia, hyperferritinemia, hypertransaminasemia, hypertriglyceridemia, immune dysregulation, intravenous drug administration, kidney dysfunction, liver function, male, multiple organ failure, poikilocytosis, secondary hemophagocytic lymphohistiocytosis, side effect, sphincterotomy, therapy, thrombocytopenia

Abstract

CASE: A 76-year-old male with a Crohn's disease on infliximab presented with fatigue and high-grade fevers. He denied sick contacts or recent travel. On presentation, he was febrile (102.5°F) but otherwise stable. Laboratory workup revealed anemia (hemoglobin 9.8 g/dL), thrombocytopenia (platelets 84 K/uL), acute kidney injury (Cr 1.89 mg/dL), elevated transaminases (AST 92 IU/L, ALT 113 IU/L, ALP 302 IU/L), hyperbilirubinemia (total 3.3 mg/dL), elevated C-reactive protein (8.5 mg/ dL), negative HIV and blood cultures. Imaging showed bowel wall thickening consistent with Crohn's and no biliary obstruction. Empiric antibiotics were started for presumed biliary infection. Persistent fevers led to endoscopic retrograde cholangiopancreatography, revealing choledocholithiasis, treated with sphincterotomy and stenting. Despite interventions, fevers persisted with rising bilirubin. A positive 1,3-beta-D-glucan assay prompted broader antibiotics. Peripheral smear showed immature precursors with poikilocytosis. Other notable findings included two-lineage cytopenias, hypertriglyceridemia (905mg/dL), hyperferritinemia (14,492 ng/mL), and low fibrinogen (157 mg/dL). Hematology raised concern for hemophagocytic lymphohistocytosis (HLH). Bone marrow biopsy revealed normocellular marrow with frequently seen hemophagocytosis. An H score of 235 and high Interleukin-2 receptor (CD25) (26,252.9 pg/ mL) further supported the diagnosis. Steroids per HLH-94 protocol were initiated; etoposide was deferred due to liver and kidney dysfunction. Despite this, liver function worsened with mental status changes. Urine antigens for histoplasmosis were positive, with disseminated disease suspected as the HLH trigger. Amphotericin B was initiated but stopped due to renal dysfunction. His condition deteriorated, leading to eventual death. IMPACT/DISCUSSION: HLH is a rare, life-threatening syndrome characterized by immune hyperactivity leading to multi-organ failure. Secondary HLH is often triggered by infections, malignancy, or autoimmunity. Diagnosis requires high suspicion due to overlap with other conditions. Hallmark features include fever, cytopenias, hepatosplenomegaly, hyperferritinemia, and coagulopathy. This case illustrates HLH triggered by disseminated histoplasmosis in an immunocompromised host. Therapy led to partial improvement, but antifungal therapy complicated treatment, underscoring the balance needed in managing HLH and its triggers. This case adds to the literature by emphasizing the importance of recognizing histoplasmosis as a potential cause of HLH, even in nonendemic settings, and highlights the need for a high index of suspicion in patients with immune dysregulation. CONCLUSION: - Persistent fever, cytopenias, hyperferritinemia, and organ dysfunction should raise suspicion for HLH. - Treatment for HLH secondary to opportunistic infections includes empiric antibiotics directed against the suspected organism and HLH specific chemotherapy.

Volume

40

First Page

S113

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